Combinations of tumor-associated antigens in diagnostics for various types of cancers

Abstract

Disclosed herein are methods for matching a cancer condition with an appropriate immunotherapeutic agent and/or regimen. Also disclosed are methods for confirming diagnosis of a particular type of cancer. Embodiments of the invention disclosed herein are directed to the use of effective combinations of TuAAs to optimize the match between a patient's cancer condition and available immunotherapies.

1 . A method of matching a cancer condition in a patient with an immunotherapeutic regimen, comprising the steps of:
 assaying the patient's tumor tissue for two or more expressed tumor-associated antigens (TuAAs) in a preselected panel, wherein the two or more TuAAs include an antigen expressed by a tumor-associated stromal cell, to develop an antigen profile for the tumor; and   selecting an immunotherapeutic regimen based on the profile, the regimen comprising administration of one or more immunotherapeutic agents, wherein said one or more immunotherapeutic agents are available on the market on in clinical trials, and wherein said one or more immunotherapeutic agents target two or more antigens in the profile.   
     
     
         2 . The method of  claim 1 , wherein at least one of the TuAAs is selected from the group consisting of a cancer testis antigen, a tissue-specific antigen, an oncofetal antigen, a differentiation antigen, a growth factor, a growth factor receptor, an adhesion factor, a signal transduction protein, a transcription factor, an oncogene product, a tumor suppressor gene product, and a microbial antigen. 
     
     
         3 . The method of  claim 1 , wherein the cancer condition is carcinoma. 
     
     
         4 . The method of  claim 3 , wherein the carcinoma is selected from the group consisting of breast, colorectal, prostate, pancreatic, lung, ovarian, renal cell, and melanocyte. 
     
     
         5 . The method of  claim 1 , wherein the immunotherapeutic agent is an active immunotherapuetic. 
     
     
         6 . The method of  claim 1 , wherein the immunotherapeutic agent comprises or encodes at least a segment of at least one of the expressed TuAAs. 
     
     
         7 . The method of  claim 1 , wherein the immunotherapeutic agent is a passive immunotherapeutic. 
     
     
         8 . The method of  claim 7 , wherein the immunotherapeutic agent is a monoclonal antibody. 
     
     
         9 . The method of  claim 1 , comprising at least two assaying steps carried out at different time points during the course of disease, wherein comparative information is obtained from the assaying steps. 
     
     
         10 . The method of  claim 9 , where the obtained information is used to implement, modify or withdraw a therapy. 
     
     
         11 . The method of  claim 1 , wherein the tumor is melanoma and the panel of TuAAs comprises at least two TuAAs selected from the group consisting of tyrosinase, melan-A/MART-1, NY-ESO-1, PRAME, an SSX protein, and a MAGE protein. 
     
     
         12 . The method of  claim 11 , wherein the SSX protein is SSX-2 or SSX-4. 
     
     
         13 . The method of  claim 11 , wherein the MAGE protein is MAGE-1 or MAGE-3. 
     
     
         14 . The method of  claim 1 , wherein the tumor is breast cancer and the panel of TuAAs comprises at least two TuAAs selected from the group consisting of NY-ESO-1, Her2/neu, an SSX protein, and a MAGE protein. 
     
     
         15 . The method of  claim 1 , wherein the tumor is colorectal cancer and the panel of TuAAs comprises at least two TuAAs selected from the group consisting of CEA, an SSX protein, PRAME, NY-ESO, LAGE, PSCA, SCP-1, PSMA and a MAGE protein. 
     
     
         16 . The method of  claim 1 , wherein the tumor is lung cancer and the panel of TuAAs comprises at least two TuAAs selected from the group consisting of PSMA, NY-ESO-1, SSX-2, and a MAGE protein. 
     
     
         17 . The method of  claim 1 , wherein the tumor is prostate cancer and the panel of TuAAs comprises at least two TuAAs selected from the group consisting of NY-ESO-1, PSA, PSCA, PSMA, an SSX protein, and a MAGE protein. 
     
     
         18 . The method of  claim 1 , wherein the tumor is ovarian cancer and the panel of TuAAs comprises at least two TuAAs selected from the group consisting of PRAME, PSMA, PSCA, a MAGE protein, SCP-1, an SSX protein, CEA, Her-2/Neu, NY-ESO-1, and LAGE. 
     
     
         19 . The method of  claim 18 , wherein the ovarian cancer is selected from the group consisting of serous carcinoma, non-serous carcinoma, mucinous (cell) carcinoma, and clear cell carcinoma. 
     
     
         20 . The method of  claim 1 , wherein the tumor is renal cancer and the panel of TuAAs comprises at least two TuAAs selected from the group consisting of an SSX protein, PRAME, NY-ESO, LAGE, PSCA, SCP-1, PSMA and a MAGE protein. 
     
     
         21 . The method of  claim 1 , wherein the tumor is pancreatic cancer and the panel of TuAAs comprises at least two TuAAs selected from the group consisting of an SSX protein, PRAME, NY-ESO, LAGE, PSCA, PSMA and a MAGE protein. 
     
     
         22 . The method of  claim 1 , wherein antigen expression is detected by a technique comprising at least one of RT-PCR, transcript determination, protein determination, epitope determination or any combination thereof. 
     
     
         23 . The method of  claim 1 , wherein antigen expression is detected on neoplastic cells, or tumor-associated stromal cells, or both. 
     
     
         24 . The method of  claim 23 , wherein the tumor-associated stromal cells are neovasculature. 
     
     
         25 . The method of  claim 24 , wherein the neovasculature-associated antigen is PSMA and the neoplastic cell antigen is selected form the group consisting of NY-ESO-1, SSX2, LAGE, and PRAME. 
     
     
         26 . The method of  claim 1 , wherein the tumor tissue comprises primary tumor tissue. 
     
     
         27 . The method of  claim 1 , wherein the tumor tissue comprises metastatic tumor tissue. 
     
     
         28 . The method of  claim 1 , wherein the regimen comprises administering both an active immunotherapeutic agent and a passive immunotherapeutic agent. 
     
     
         29 . A method of matching a cancer condition in a patient with an immunotherapeutic agent, comprising the steps of:
 determining the patient's class I MHC type;   assaying the patient's tumor tissue for two or more expressed tumor-associated antigens (TuAAs) in a preselected panel;   assaying the patient's tumor tissue for the expression of MHC class I or β2-microglobulin;   selecting an immunotherapeutic agent for administration to the patient based on the assays, wherein the immunotherapeutic agent comprises or encodes an epitope restricted by the patient's class I MHC type, for each of two or more antigens expressed by the tumor.   
     
     
         30 . The method of  claim 29 , wherein antigen expression is detected on neoplastic cells, or tumor-associated stromal cells, or both. 
     
     
         31 . The method of  claim 30 , wherein the two or more antigens expressed by the tumor include an antigen expressed by a neoplastic cell and an antigen expressed by a tumor-associated stromal cell. 
     
     
         32 . A method of confirming a cancer diagnosis comprising the steps of:
 assaying a patient's tumor tissue to detect one or more expressed polypeptides in a preselected panel, wherein the panel comprises two or more TuAAs and at least one lineage marker, to develop an expression profile for the tumor; and   confirming a cancer diagnosis based upon the expression profile.   
     
     
         33 . The method of  claim 32 , wherein the panel comprises at least three TuAAs selected from the group consisting of NY-ESO-1, CEA, PSA, PSMA, tyrosinase, melan-A/MART-1, an SSX protein, and a MAGE protein. 
     
     
         34 . The method of  claim 32 , wherein the diagnosis is melanoma and the lineage marker is selected from the group consisting of melan-A/MART-1, tyrosinase, and gp100. 
     
     
         35 . The method of  claim 32 , wherein the diagnosis is breast cancer and the lineage marker is selected from the group consisting of mammaglobin and prolactin-inducuble protein (Brst2). 
     
     
         36 . The method of  claim 32 , wherein the diagnosis is colon cancer and the lineage marker is CEA. 
     
     
         37 . The method of  claim 32 , wherein the diagnosis is lung cancer and the lineage marker is thyroid transcription factor 1 (TTF1). 
     
     
         38 . The method of  claim 32 , wherein the diagnosis is prostate cancer and the lineage marker is selected from the group consisting of PSA and PSMA. 
     
     
         39 . A method of matching a cancer condition in a patient with an immunotherapeutic agent, comprising the steps of:
 assaying tumor tissue of the patient for two or more expressed tumor-associated antigens (TuAAs) in a preselected panel, to develop an antigen profile for the tumor; and   selecting an immunotherapeutic agent for the patient based on the profile, wherein the immunotherapeutic agent targets one or more of the expressed antigens in the profile.